Leak-Free Stopper Having Low Breakloose and Sustaining Forces

ABSTRACT

A thermoplastic elastomer stopper that meets the desired material properties of a stopper for a syringe assembly is disclosed. The compression set of the thermoplastic elastomer stopper of the present disclosure is ≤50% when measured at 25% compression for 22 hrs at 70 degree C. The hardness of the thermoplastic elastomer stopper of the present disclosure is 40-70 Shore A. The viscosity of a thermoplastic elastomer stopper of the present disclosure is ≥70 Pa·s at 1,000 s −1  shear rate, ≥12.0 Pa·s at 10,000 s −1  shear rate, and ≥3.0 Pa·s at 50,000 s −1  shear rate when measured using a capillary rheometer at 205 degree C. (Die: Roundhole 20 mm length/1 mm diameter/180 degree inlet, Piston: d=15 mm, and melting time=7 min). The present non-lubricated stopper exhibits the required functional performance of a lubricated stopper.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.14/525,395, filed Oct. 28, 2014, which claims priority to U.S.Provisional Patent Application Ser. No. 61/896,332, filed Oct. 28, 2013,the entire disclosures of each of which are hereby expresslyincorporated by reference herein.

BACKGROUND OF THE INVENTION 1. Field of the Disclosure

The present disclosure relates generally to a stopper for a syringeassembly. More particularly, the present disclosure relates to athermoplastic elastomer (TPE) stopper that meets the desired materialproperties of a stopper for a syringe assembly.

2. Description of the Related Art

Syringe assemblies are well known in the medical field for dispensingfluids, such as medications. A conventional syringe typically includes asyringe barrel with an opening at one end and a plunger mechanismdisposed through the opposite end. The plunger mechanism typicallyincludes a plunger rod extending through the barrel, with a plunger heador stopper disposed at the end of the plunger rod within the syringebarrel, and with a finger flange at the other end of the plunger rodextending out of the syringe barrel. In use, the plunger rod isretracted through the syringe barrel to aspirate or fill the syringebarrel with a fluid, such as a medication, with the plunger rodextending out from the rear end of the syringe barrel. For delivery ofthe medication to a patient, the opening of the syringe barrel isadapted for fluid communication with a patient, such as through ahypodermic needle fitted at the front end of the syringe barrel orthrough a luer-type fitting extending from the syringe barrel forattachment with a fluid line of a patient. Upon the user applying aforce to depress the plunger rod and stopper through the syringe barreltowards the front end of the syringe barrel, the contents of the syringeare thereby forced out of the syringe barrel through the opening at thefront end for delivery to the patient. Such an operation is well knownin the medical field, and medical practitioners have become wellaccustomed to the use of such common fluid delivery procedures throughstandard syringes.

Syringe assemblies require slow and controlled initiation andmaintenance of sliding movement of one surface over another surface. Itis well known that two stationary surfaces having a sliding relationshipoften exhibit sufficient resistance to initiation of movement thatgradually increased pressure applied to one of the surfaces does notcause movement until a threshold pressure is reached, at which point asudden sliding separation of the surfaces takes place. This suddenseparation of stationary surfaces into a sliding relationship is hereinreferred to as “breakout”.

A less well known, but important frictional force is “breakloose force”,which refers to the force required to overcome static friction betweensurfaces of a syringe assembly that has been subjected to sterilization(including autoclaving or other processes) and may have a slightdeformation in one or both of the contacting surfaces of the syringeassembly, for example in the syringe barrel. In addition to autoclaving,parking of the assembly can further increase the breakloose force.

Breakout and breakloose forces are particularly troublesome in liquiddispensing devices, such as syringes, used to deliver small, accuratelymeasured quantities of a liquid by smooth incremental line-to-lineadvancement of one surface over a graduated second surface. The problemis also encountered in devices using stopcocks, such as burets, pipets,addition funnels, and the like where careful dropwise control of flow isdesired.

A critical performance requirement of a stopper is achieving high leakpressure, i.e., the ability of a stopper to maintain a leak-free syringewhile maintaining low breakloose and sustaining forces.

The problems of excessive breakout and breakloose forces are related tofriction. Friction is generally defined as the resisting force thatarises when a surface of one substance slides, or tends to slide, overan adjoining surface of itself or another substance. Between surfaces ofsolids in contact, there may be two kinds of friction: (1) theresistance opposing the force required to start to move one surface overanother, conventionally known as static friction, and (2) the resistanceopposing the force required to move one surface over another at avariable, fixed, or predetermined speed, conventionally known as kineticfriction.

The force required to overcome static friction and induce breakout isreferred to as the “breakout force”, and the force required to maintainsteady slide of one surface over another after breakout or breakloose isreferred to as the “sustaining force”. Two main factors contribute tostatic friction and thus to the breakout or breakloose force. The term“stick” as used herein denotes the tendency of two surfaces instationary contact to develop a degree of adherence to each other. Theterm “inertia” is conventionally defined as the indisposition to motionwhich must be overcome to set a mass in motion. In the context of thepresent invention, inertia is understood to denote that component of thebreakout force which does not involve adherence.

Breakout or breakloose forces, in particular the degree of stick, varyaccording to the composition of the surfaces. In general, materialshaving elasticity show greater stick than non-elastic materials,particularly when the surfaces are of similar composition. The length oftime that surfaces have been in stationary contact with each other alsoinfluences breakout and/or breakloose forces. In the syringe art, theterm “parking” denotes storage time, shelf time, or the interval betweenfilling and discharge. Parking generally increases breakout orbreakloose force, particularly if the syringe has been refrigeratedduring parking.

A conventional approach to overcoming breakout has been application of alubricant to a surface-to-surface interface. Such conventionallubricated stoppers have the disadvantage of being soluble in a varietyof fluids, such as vehicles commonly used to dispense medicaments. Inaddition, these lubricants are subject to air oxidation resulting inviscosity changes and objectionable color development. Further, they areparticularly likely to migrate from the surface-to-surface interface.Such lubricant migration is generally thought to be responsible for theincrease in breakout force with time in parking.

Additional problems with applying a lubricant to a surface of a stopperis that such a lubrication step requires costs in lubricants and lubinginstruments, time and energy to operate and perform the lubricationstep, and the stopper must be removed from an automated assembly processto be lubricated.

For these reasons, there is a need for a better syringe assembly systemto overcome high breakout and breakloose forces whereby smoothtransition of two surfaces from stationary contact into sliding contactcan be achieved and there is a need for a stopper that exhibits therequired performance characteristics and that does not require theadditional lubrication step.

SUMMARY OF THE INVENTION

The present disclosure provides for a thermoplastic elastomer stopperthat meets the desired material properties of a stopper for a syringeassembly. These material properties are compression set, hardness,stress at given strain levels, and viscosity at given shear rates. Thecompression set of a thermoplastic elastomer stopper of the presentdisclosure may be ≤50% when measured at 25% compression for 22 hrs at 70degrees C. (ASTM D395-03, Method B). The hardness of a thermoplasticelastomer stopper of the present disclosure may be in the range of 40-70Shore A (ASTM D2240-05). The stress at desired strain values should alsobe optimized for the thermoplastic elastomer stopper of the presentdisclosure so as to obtain good leak and force performance with theassembled syringe. The viscosity of a thermoplastic elastomer stopper ofthe present disclosure may be ≥70.0 Pa·s at 1,000 s⁻¹ shear rate, ≥12.0Pa·s at 10,000 s⁻¹ shear rate, and ≥3.0 Pa·s at 50,000 s⁻¹ shear ratewhen measured using a capillary rheometer at 205 degrees C. (Die:Roundhole 20 mm length/1 mm diameter/180 degree inlet, Piston: d=15 mm,and melting time=7 min). In one embodiment, a thermoplastic elastomerstopper of the present disclosure provides for sticktion-freeperformance with a polypropylene or polypropylene copolymer basedbarrel. For example, a stopper of the present disclosure includes a30-65% elastomer such as but not limited to 30-65%styrene-ethylene-butylene-styrene (SEBS) copolymer blended with 10-35%medium to high density polyethylene (medium to high density with meltingtemperature in the range of 120 degrees C. to 130 degrees C.), 20-35%commonly available mineral oil along with commonly available radiationstabilizer, antioxidant, and/or processing aid. The molecular weight ofthe elastomer and polyethylene are selected so as to obtain the desiredmaterial properties as described above.

The present disclosure also provides a stopper that maintains aleak-free syringe with low breakloose and sustaining forces. In oneembodiment, the present disclosure provides a non-lubricated stopperthat exhibits the required functional performance factors for a syringeassembly. Advantageously, the stopper of the present disclosure providesthe required functional performance while eliminating the externallubricant application on a stopper. In this manner, the negativeconsequences of the external lubricant application on a stopper areeliminated. For example, the lubrication step on a stopper requirescosts in lubricants and lubing instruments, time and energy to operateand perform the lubrication step, and the stopper must be removed froman automated assembly process to be lubricated. The non-lubricatedstopper of the present disclosure also provides a stopper which allowsfor a complete automation stopper assembly process. Additionally, astopper of the present disclosure allows for an autoclavablenon-lubricated stopper for a syringe assembly by use of a high meltingtemperature polymer as the hard phase.

The present invention provides a stopper for a syringe assembly havingan exterior surface adapted to sealingly engage an inner surface of achamber of a medical device. The respective surfaces can be infrictional engagement. When used in a medical device, the stopper of thepresent invention can reduce the force required to achieve breakout,breakloose, and/or sustaining forces, whereby transition of surfacesfrom stationary contact to sliding contact occurs without a suddensurge. When breakout or breakloose is complete and the surfaces are insliding contact, they slide smoothly upon application of very lowsustaining force. These advantages are achieved without the use of alubricant being applied to a surface of the stopper. The presentinvention also provides a stopper which achieves high leak pressure. Inthis manner, the stopper of the present disclosure maintains a leak-freesyringe with low breakloose and sustaining forces. The effect achievedby the stopper of the present disclosure and methods of the presentinvention can provide the advantages of leak-free, low breakout, lowbreakloose, and sustaining forces throughout any parking period. Whenthe stopper of the present disclosure is part of a liquid dispensingdevice such as a syringe assembly, small highly accurate increments ofliquid may be dispensed repeatedly without sudden surges. Thus, asyringe assembly including a stopper of the present disclosure can beused to administer a medicament to a patient without the danger ofsurges whereby accurate control of dosage and greatly enhanced patientsafety are realized. This is achieved and maintained after sterilizationand over the lifetime of the stopper, e.g., five (5) years.

In accordance with an embodiment of the present invention, a stopper fora syringe assembly includes a thermoplastic elastomer, wherein thecompression set of the thermoplastic elastomer is ≤50% when measured at25% compression for 22 hrs at 70 degrees C., wherein the hardness of thethermoplastic elastomer is approximately 40-70 Shore A, and wherein theviscosity of the thermoplastic elastomer is ≥70.0 Pa·s at 1,000 s⁻¹shear rate, ≥12.0 Pa·s at 10,000 s⁻¹ shear rate, and ≥3.0 Pa·s at 50,000s⁻¹ shear rate when measured using a capillary rheometer at 205 degreesC. (Die: Roundhole 20 mm length/1 mm diameter/180 degree inlet, Piston:d=15 mm, and melting time=7 min).

In one configuration, the compression set of the thermoplastic elastomeris approximately ≤35% when measured at 25% compression for 22 hrs at 70degrees C. In another configuration, the compression set of thethermoplastic elastomer is approximately 10%-35% when measured at 25%compression for 22 hrs at 70 degrees C. In yet another configuration,the hardness of the thermoplastic elastomer is approximately 45-65 ShoreA. In one configuration, the hardness of the thermoplastic elastomer isapproximately 53-63 Shore A. In another configuration, the viscosity ofthe thermoplastic elastomer is 70.0 Pa·s-320.0 Pa·s at 1,000 s⁻¹ shearrate. In yet another configuration, the viscosity of the thermoplasticelastomer is 100.0 Pa·s-170.0 Pa·s at 1,000 s⁻¹ shear rate. In oneconfiguration, the viscosity of the thermoplastic elastomer is 12.0Pa·s-46.0 Pa·s at 10,000 s⁻¹ shear rate. In another configuration, theviscosity of the thermoplastic elastomer is 16.0 Pa·s-27.0 Pa·s at10,000 s⁻¹ shear rate. In yet another configuration, the viscosity ofthe thermoplastic elastomer is 3.0 Pa·s-12.0 Pa·s at 50,000 s⁻¹ shearrate. In one configuration, the viscosity of the thermoplastic elastomeris 4.5 Pa·s-7.5 Pa·s at 50,000 s⁻¹ shear rate.

In accordance with another embodiment of the present invention, asyringe assembly includes a syringe barrel having a proximal end, adistal end, and a sidewall extending therebetween and defining a chamberhaving an interior, the syringe barrel formed of a first material and astopper slidably disposed within the interior of the chamber of thesyringe barrel, the stopper sized relative to the interior of thechamber of the syringe barrel to provide sealing engagement with thesidewall of the syringe barrel, the stopper formed of a second materialdifferent than the first material, wherein the second material does notcontain more than 4% of the first material and more preferably thesecond material does not contain more than 1.5% of the first materialand still more preferably the second material does not contain more than1% of the first material. The syringe assembly further includes aplunger rod having a first end engageable with a portion of the stopper.

In accordance with another embodiment of the present invention, asyringe assembly includes a syringe barrel having a proximal end, adistal end, and a sidewall extending therebetween and defining a chamberhaving an interior and a stopper slidably disposed within the interiorof the chamber of the syringe barrel, the stopper sized relative to theinterior of the chamber of the syringe barrel to provide sealingengagement with the sidewall of the syringe barrel, the stopper formedof a non-lubricated thermoplastic elastomer. The syringe assemblyfurther includes a plunger rod having a first end engageable with aportion of the stopper.

In one configuration, the stopper includes a polyethylene blended withstyrene block copolymer. In another configuration, the stopper includesan olefin block copolymer containing polyethylene blocks. The stoppercomposition can also include mineral oil, radiation stabilizer,antioxidant, and/or processing aids.

In accordance with another embodiment of the present invention, asyringe assembly includes a syringe barrel having a proximal end, adistal end, and a sidewall extending therebetween and defining a chamberhaving an interior, the syringe barrel formed of a barrel material. Thesyringe assembly further includes a stopper including a thermoplasticelastomer, wherein the compression set of the thermoplastic elastomer is≤50% when measured at 25% compression for 22 hrs at 70 degrees C.,wherein the hardness of the thermoplastic elastomer is 40-70 Shore A,and wherein the viscosity of the thermoplastic elastomer is ≥70.0 Pa·sat 1,000 s⁻¹ shear rate, ≥12.0 Pa·s at 10,000 s⁻¹ shear rate, and ≥3.0Pa·s at 50,000 s⁻¹ shear rate, the stopper including a formulationincluding an elastomeric phase such as but not limited to styrene blockcopolymer, olefin block copolymer, SBR rubber, or polyisoprene and mayhave a hard polymer phase such as polyolefin, for example, but notlimited to, polyethylene and other higher melting temperature polymer(>170 degrees C.) such as ethylene-tetra-fluoro-ethylene and fluorinatedethylene propylene polymers along with hydrocarbon liquids such asmineral oil and radiation stabilizer, antioxidant, and/or otherprocessing aids, the stopper slidably disposed within the interior ofthe chamber of the syringe barrel, the stopper sized relative to theinterior of the chamber of the syringe barrel to provide sealingengagement with the sidewall of the syringe barrel, the stopper formedof a non-lubricated thermoplastic elastomer. The syringe assemblyfurther includes a plunger rod having a first end engageable with aportion of the stopper, wherein the formulation of the stopper isdifferent than the barrel material, for example, the hard phase for theformulation of the stopper should not be polypropylene based in case ofthe barrel material being formed of polypropylene or polypropylene basedbarrels.

In accordance with another embodiment of the present invention, astopper of the present invention provides advantages relating tomanufacturing and/or molding. For example, in one embodiment, a stopperof the present invention includes a shear-feature, i.e., a thin-wallsection, at the mold gating point within a mold cavity. Theshear-feature of a stopper of the present invention adds shear heat atthe mold gate point. In this manner, a stopper of the present inventioneliminates cold material from entering the mold cavity, eliminates flowlines and/or weld lines common to stopper molding, eliminates sinkmarks, improves the control of gate quality, improves the mold cycletime, and eliminates surface and/or visual imperfections.

In accordance with another embodiment of the present invention, astopper for a syringe assembly includes a lower portion, a roof portionhaving a first thickness, and a shear element disposed adjacent the roofportion, the shear element having a second thickness, wherein the secondthickness of the shear element is less than 52% and greater than 36% ofthe first thickness of the roof portion.

In one configuration, the second thickness of the shear element isapproximately 44% of the first thickness of the roof portion. In anotherconfiguration, the stopper includes a catch can element having areceiving volume.

In accordance with another embodiment of the present invention, astopper for a syringe assembly includes a lower portion; a roof portion;a core portion disposed adjacent the roof portion, the core portionhaving a semi-ellipsoidal shape; a first sealing rib disposed adjacentthe roof portion; and a second sealing rib disposed adjacent the lowerportion.

In one configuration, the first sealing rib is configured to provide anincreased contact pressure at the first sealing rib as a fluid pressureincreases. In one embodiment, a first rib width results into lowerbreakout and sustaining forces along with acceptable compression setduring the syringe shelf life. In another configuration, a slip additiveis added to the thermoplastic elastomer.

In accordance with another embodiment of the present invention, astopper of the present disclosure can be used with an unlubed barrelthat has been modified with a slip agent. The slip agent may be acombination of a slow blooming component for long term performance and afast blooming component which reduces friction properties faster.

In accordance with another embodiment of the present invention, astopper for a syringe assembly includes a lower portion; a roof portion,the roof portion having a first thickness; a shear element disposedadjacent the roof portion, the shear element having a second thickness,wherein the second thickness of the shear element is less than 52% andgreater than 36% of the first thickness of the roof portion; and a catchcan element having a receiving volume.

In accordance with another embodiment of the present invention, asyringe assembly includes a syringe barrel having a proximal end, adistal end, and a sidewall extending therebetween and defining a chamberhaving an interior, the syringe barrel having a barrel materialformulation; a stopper comprising a thermoplastic elastomer, wherein thecompression set of the thermoplastic elastomer is ≤50% when measured at25% compression for 22 hrs at 70 degrees C., wherein the hardness of thethermoplastic elastomer is 40-70 Shore A, and wherein the viscosity ofthe thermoplastic elastomer is ≥70.0 Pa·s at 1,000 s⁻¹ shear rate, ≥12.0Pa·s at 10,000 s⁻¹ shear rate, and ≥3.0 Pa·s at 50,000 s⁻¹ shear rate,the stopper comprising a formulation having a hard polymer phase havinga high melt temperature >170 degrees C., the stopper slidably disposedwithin the interior of the chamber of the syringe barrel, the stoppersized relative to the interior of the chamber of the syringe barrel toprovide sealing engagement with the sidewall of the syringe barrel, thestopper formed of a non-lubricated thermoplastic elastomer; and aplunger rod having a first end engageable with a portion of the stopper,wherein the formulation of the stopper is different than the barrelmaterial formulation.

BRIEF DESCRIPTION OF THE DRAWINGS

The above-mentioned and other features and advantages of thisdisclosure, and the manner of attaining them, will become more apparentand the disclosure itself will be better understood by reference to thefollowing descriptions of embodiments of the disclosure taken inconjunction with the accompanying drawings, wherein:

FIG. 1 is an assembled plan view of a syringe assembly including astopper in a first position in accordance with an embodiment of thepresent invention.

FIG. 2A is a cross-sectional view of the syringe assembly of FIG. 1 withthe stopper in a second position in accordance with an embodiment of thepresent invention.

FIG. 2B is a detailed view of a portion of a stopper in contact with aninterior surface of a syringe barrel in accordance with an embodiment ofthe present invention.

FIG. 3 is a plan view of a stopper in accordance with an embodiment ofthe present invention.

FIG. 4 is a cross-sectional view taken along line 4-4 of FIG. 3 inaccordance with an embodiment of the present invention.

FIG. 5 is a cross-sectional view taken along line 5-5 of FIG. 3 inaccordance with an embodiment of the present invention.

FIG. 6 is a plan view of a stopper in accordance with another embodimentof the present invention.

FIG. 7 is a cross-sectional view taken along line 7-7 of FIG. 6 inaccordance with another embodiment of the present invention.

FIG. 8 is a cross-sectional view taken along line 8-8 of FIG. 6 inaccordance with another embodiment of the present invention.

FIG. 9 is a graph of a conventional stopper exhibiting sticktion inaccordance with an embodiment of the present invention.

FIG. 10 is a graph of a stopper that does not exhibit sticktion inaccordance with an embodiment of the present invention.

FIG. 11 is a table comparing the stress-strain properties of variousstoppers in accordance with an embodiment of the present invention.

FIG. 12 is a table comparing functional properties of various stoppersin accordance with an embodiment of the present invention.

FIG. 13 is a table comparing functional properties of various stoppersin accordance with an embodiment of the present invention.

FIG. 14A is a graph of the viscosity and shear rate of various stoppersin accordance with an embodiment of the present invention.

FIG. 14B is a table of the hand control properties of various stoppersin accordance with an embodiment of the present invention.

FIG. 15 is a table comparing contact pressure values of a conventionalstopper with a stopper at a first sealing rib of the stopper inaccordance with an embodiment of the present invention.

FIG. 16 is a table of various thermoplastic elastomer stoppers inaccordance with an embodiment of the present invention.

FIG. 17 is a table of the polypropylene (PP) content of variousthermoplastic elastomer stoppers in accordance with an embodiment of thepresent invention.

FIG. 18 is a graph of a pump force profile of a thermoplastic elastomerstopper in accordance with an embodiment of the present invention.

FIG. 19 is a graph of a pump force profile of a thermoplastic elastomerstopper in accordance with an embodiment of the present invention.

FIG. 20 is a table of the polypropylene (PP) content, polyethylene (PE)content, compression set, and leak performance of various thermoplasticelastomer stoppers in accordance with an embodiment of the presentinvention.

FIG. 21 is a table of the polypropylene (PP) content, polyethylenecontent (PE), compression set, viscosity at specific shear rates, andhand controls of various thermoplastic elastomer stoppers in accordancewith an embodiment of the present invention.

FIG. 22 is a table of the force performance of a thermoplastic elastomerstopper with different levels of an Erucamide slip agent in accordancewith an embodiment of the present invention.

FIG. 23 is a table of the leak pressure and sustaining force rankingsfor thermoplastic elastomer stoppers as predicted by FEA simulation inaccordance with an embodiment of the present invention.

FIG. 24 is a table of the experimental values of leak pressure andsustaining force rankings for thermoplastic elastomer stoppers inaccordance with an embodiment of the present invention.

FIG. 25 is a table of material properties for thermoplastic elastomerstoppers in accordance with an embodiment of the present invention.

FIG. 26 is a table of the hand controls of thermoplastic elastomerstoppers with different levels of an Erucamide slip agent in accordancewith an embodiment of the present invention.

FIG. 27 is a cross-sectional view of a thermoplastic elastomer stopperand a hot-tip portion of a hot runner system in accordance with anembodiment of the present invention.

FIG. 28 is a cross-sectional view of a thermoplastic elastomer stopperand a hot-tip portion of a hot runner system in accordance with anembodiment of the present invention.

Corresponding reference characters indicate corresponding partsthroughout the several views. The exemplifications set out hereinillustrate exemplary embodiments of the disclosure, and suchexemplifications are not to be construed as limiting the scope of thedisclosure in any manner.

DETAILED DESCRIPTION

Other than in the operating examples, or where otherwise indicated, allnumbers expressing quantities of ingredients, material properties, andso forth used in the specification and claims and Figures are to beunderstood as being modified in all instances by the term “about”.Accordingly, unless indicated to the contrary, the numerical parametersset forth in the following specification and attached claims areapproximations that may vary depending upon the desired propertiessought to be obtained by the present invention. At the very least, andnot as an attempt to limit the application of the doctrine ofequivalents to the scope of the claims, each numerical parameter shouldat least be construed in light of the number of reported significantdigits and by applying ordinary rounding techniques.

Notwithstanding that the numerical ranges and parameters setting forththe broad scope of the invention are approximations, the numericalvalues set forth in the specific examples are reported as precisely aspossible. Any numerical value, however, inherently contains certainerrors necessarily resulting from the standard deviation found in theirrespective testing measurements. Furthermore, when numerical ranges ofvarying scope are set forth herein, it is contemplated that anycombination of these values inclusive of the recited values may be used.

For purposes of the description hereinafter, the terms “upper”, “lower”,“right”, “left”, “vertical”, “horizontal”, “top”, “bottom”, “lateral”,“longitudinal”, and derivatives thereof shall relate to the invention asit is oriented in the drawing figures. However, it is to be understoodthat the invention may assume various alternative variations, exceptwhere expressly specified to the contrary. It is also to be understoodthat the specific devices illustrated in the attached drawings, anddescribed in the following specification, are simply exemplaryembodiments of the invention. Hence, specific dimensions and otherphysical characteristics related to the embodiments disclosed herein arenot to be considered as limiting.

In the following discussion, “distal” refers to a direction generallytoward an end of a syringe assembly adapted for contact with a patientand/or engagement with a separate device such as a needle assembly or IVconnection assembly, and “proximal” refers to the opposite direction ofdistal, i.e., away from the end of a syringe assembly adapted forengagement with the separate device. For purposes of this disclosure,the above-mentioned references are used in the description of thecomponents of a syringe assembly in accordance with the presentdisclosure.

The present disclosure provides for a thermoplastic elastomer stopperthat meets the desired material properties of a stopper for a syringeassembly. These material properties are compression set, hardness,stress at given strain levels, and viscosity at given shear rates. Thecompression set of a thermoplastic elastomer stopper of the presentdisclosure may be ≤50% when measured at 25% compression for 22 hrs at 70degrees C. (ASTM D395-03, Method B). The hardness of a thermoplasticelastomer stopper of the present disclosure may be in the range of 40-70Shore A (ASTM D2240-05). The stress at desired strain values should alsobe optimized for the thermoplastic elastomer stopper of the presentdisclosure so as to obtain good leak and force performance with theassembled syringe. The viscosity of a thermoplastic elastomer stopper ofthe present disclosure may be ≥70.0 Pa·s at 1,000 s⁻¹ shear rate, ≥12.0Pa·s at 10,000 s⁻¹ shear rate, and ≥3.0 Pa·s at 50,000 s⁻¹ shear ratewhen measured using a capillary rheometer at 205 degrees C. (Die:Roundhole 20 mm length/1 mm diameter/180 degree inlet, Piston: d=15 mm,and melting time=7 min). In one embodiment, a thermoplastic elastomerstopper of the present disclosure provides for sticktion-freeperformance with a polypropylene or polypropylene copolymer basedbarrel. For example, a stopper of the present disclosure includes a30-65% elastomer such as but not limited to 30-65%styrene-ethylene-butylene-styrene (SEBS) copolymer blended with 10-35%medium to high density polyethylene (medium to high density with meltingtemperature in the range of 120 degree C. to 130 degrees C.), 20-35%commonly available mineral oil along with commonly available radiationstabilizer, antioxidant, and/or processing aids. The molecular weight ofthe elastomer and polyethylene are selected so as to obtain the desiredmaterial properties as described above.

The present disclosure also provides a stopper that maintains aleak-free syringe with low breakloose and sustaining forces. In oneembodiment, the present disclosure provides a non-lubricated stopperthat exhibits the required functional performance factors for a syringeassembly. Advantageously, the stopper of the present disclosure providesthe required functional performance while eliminating the externallubricant application on a stopper. In this manner, the negativeconsequences of the external lubricant application on a stopper areeliminated. For example, the lubrication step on a stopper requirescosts in lubricants and lubing instruments, time and energy to operateand perform the lubrication step, and the stopper must be removed froman automated assembly process to be lubricated. The non-lubricatedstopper of the present disclosure also provides a stopper which allowsfor a complete automation stopper assembly process. Additionally, astopper of the present disclosure allows for an autoclavablenon-lubricated stopper for a syringe assembly by use of a high meltingtemperature polymer as the hard phase. For example, referring to FIG.16, multiple different formulations of a stopper of the presentdisclosure are provided, which are referenced throughout the presentdisclosure. The formulations include various TPE chemistry such asolefin block copolymer, polyethylene blended with styrenic blockcopolymer, polypropylene blended with styrenic block copolymer, andpolyethylene blended with EPDM TPV. These TPE formulations may containcommonly available radiation stabilizer, antioxidant, and/or processingaids.

In a first exemplary embodiment, a stopper of the present disclosure isformed of an olefin block copolymer, e.g., a TPE-1 embodiment. In asecond exemplary embodiment, a stopper of the present disclosure isformed of a polyethylene blended with styrenic block copolymer having afirst composition, e.g., a TPE-2 embodiment. In a third exemplaryembodiment, a stopper of the present disclosure is formed of apolyethylene blended with styrenic block copolymer having a secondcomposition, e.g., a TPE-3 embodiment. In a fourth exemplary embodiment,a stopper of the present disclosure is formed of a polypropylene blendedwith styrene block copolymer formulation with a lower viscosity than theTPE-1 and TPE-2 embodiments, e.g., a TPE-4 embodiment. In a fifthexemplary embodiment, a stopper of the present disclosure is formed of apolyethylene blended with styrenic block copolymer having a thirdcomposition, e.g., a TPE-5 embodiment. In other exemplary embodiments, astopper of the present disclosure is formed of other materials and/orformulations, e.g., multiple different exemplary formulations of astopper of the present disclosure are provided in FIG. 16.

In accordance with another embodiment of the present invention, astopper of the present disclosure can be used with an unlubricatedbarrel that has been modified with a slip agent. The slip agent may be acombination of a slow blooming component for long term performance and afast blooming component which reduces friction properties faster.

Referring to FIGS. 1 and 2A, a syringe assembly 10 includes a syringebarrel 12, a plunger rod 14, and a stopper 16. Syringe assembly 10 maybe adapted for dispensing and delivery of a fluid and/or collection of afluid. For example, syringe assembly 10 may be used for injection orinfusion of fluid such as a medication into a patient. Syringe assembly10 is contemplated for use in connection with a needle, such as byconnecting syringe assembly 10 to a separate needle assembly (notshown), or alternatively for connection with an intravenous (IV)connection assembly (not shown). It can be appreciated that the presentdisclosure can be used with any type of syringe assembly. These types ofsyringes include traditional pre-filled syringe assemblies, metered dosesyringes, aspiration syringes for withdrawing fluid from a patient ormedication from a container, and the like.

Referring to FIGS. 1 and 2A, syringe barrel 12 generally includes abarrel body or sidewall 30 extending between a first or distal end 32and a second or proximal end 34. Sidewall 30 defines an elongateaperture or interior chamber 36 of syringe barrel 12. In one embodiment,interior chamber 36 may span the extent of syringe barrel 12 so thatsyringe barrel 12 is cannulated along its entire length. In oneembodiment, syringe barrel 12 may be in the general form of an elongatedcylindrical barrel as is known in the art in the general shape of ahypodermic syringe. In alternative embodiments, syringe barrel 12 may bein other forms for containing a fluid for delivery, such as in thegeneral form of an elongated rectangular barrel, for example. Syringebarrel 12 may be formed of glass, or may be injection molded fromthermoplastic material such as polypropylene, polyethylene,cycloaliphatic polyolefins, polyesters, or polycarbonate, for example,according to techniques known to those of ordinary skill in the art,though it is to be appreciated that syringe barrel 12 may be made fromother suitable materials and according to other applicable techniques.In certain configurations, syringe barrel 12 may include an outwardlyextending flange 40 about at least a portion of proximal end 34. Flange40 may be configured for easy grasping by a medical practitioner.

Distal end 32 of syringe barrel 12 includes outlet opening 38 which isin fluid communication with chamber 36. Outlet opening 38 may be sizedand adapted for engagement with a separate device, such as a needleassembly or IV connection assembly and, therefore, may include amechanism for such engagement as is conventionally known. For example,distal end 32 may include a generally-tapered luer tip 42 for engagementwith an optional separate tapered luer structure of such a separatedevice for attachment therewith (not shown). In one configuration, boththe tapered luer tip 42 and the separate tapered luer structure may beprovided with syringe assembly 10. In such a configuration, the separatetapered luer structure may be fitted with an attachment mechanism, suchas a threaded engagement, for corresponding engagement with a separatedevice (not shown). In another configuration, tapered luer tip 42 may beprovided for direct engagement with a separate device (not shown). Inaddition, a mechanism for locking engagement therebetween may also beprovided with at least one of tapered luer tip 42 and/or the separatetapered luer structure, such as a luer collar or luer lock includinginterior threads. Such luer connections and luer locking mechanisms arewell known in the art.

Proximal end 34 of syringe barrel 12 is generally open-ended, but isintended to be closed off to the external environment as discussedherein. Syringe barrel 12 may also include markings 44, such asgraduations located on sidewall 30, for providing an indication as tothe level or amount of fluid contained within interior chamber 36 ofsyringe barrel 12. Such markings 44 may be provided on an externalsurface of sidewall 30, an internal surface of sidewall 30, orintegrally formed or otherwise within sidewall 30 of syringe barrel 12.In other embodiments, alternatively, or in addition thereto, themarkings 44 may also provide a description of the contents of thesyringe or other identifying information as may be known in the art,such as maximum and/or minimum fill lines.

Syringe assembly 10 may be useful as a pre-filled syringe, and,therefore, may be provided for end use with a fluid, such as amedication or drug, contained within interior chamber 36 of syringebarrel 12, pre-filled by the manufacturer. In this manner, syringeassembly 10 can be manufactured, pre-filled with a medication, andsterilized for delivery, storage, and use by the end user, without theneed for the end user to fill the syringe with medication from aseparate vial prior to use. In such an embodiment, syringe assembly 10may include a cap or sealing member disposed at distal end 32 of syringebarrel 12 to seal a fluid, such as a medication, within interior chamber36 of syringe barrel 12.

Referring to FIGS. 1-2B, syringe assembly 10 includes stopper 16 whichis moveably or slidably disposed within interior chamber 36, and is insealing contact with the internal surface of sidewall 30 of syringebarrel 12. Stopper 16 is sized relative to the interior of syringebarrel 12 to provide sealing engagement with the interior surface ofsidewall 30 of syringe barrel 12. In a pre-filled syringe assembly,stopper 16 also provides a seal to prevent liquid or medication fromleaking out of syringe barrel 12. Additionally, in one embodiment,stopper 16 may include one or more annular ribs extending around theperiphery of stopper 16 to increase the sealing engagement betweenstopper 16 and the interior surface of sidewall 30 of syringe barrel 12.In alternate embodiments, a singular O-ring or a plurality of O-ringsmay be circumferentially disposed about stopper 16 to increase thesealing engagement with the interior surface of sidewall 30.

Referring to FIGS. 1 and 2A, syringe assembly 10 further includesplunger rod 14 which provides a mechanism for dispensing fluid containedwithin interior chamber 36 of syringe barrel 12 through outlet opening38. Plunger rod 14 is adapted for advancing stopper 16. In oneembodiment, plunger rod 14 is sized for movement within interior chamber36 of syringe barrel 12 as will be discussed in more detail below, andgenerally includes a first or distal end 60 engageable with a portion ofstopper 16, a second or proximal end 62, a plunger rod body 64 extendingbetween first end 60 and second end 62, and a flange 66 disposedadjacent second end 62.

Referring to FIGS. 1 and 2A, plunger rod 14 includes a distal end 60that is engageable with a portion of stopper 16. In one embodiment,plunger rod 14 and stopper 16 may include engagement portions forsecuring plunger rod 14 to stopper 16. For example, the engagementportions may include corresponding threaded portions for securingplunger rod 14 to stopper 16. In other embodiments, the engagementportions may include a snap fit mechanism, a press-fit mechanism, a balldetent, locking tabs, spring loaded locking mechanism, latch, adhesive,or other similar mechanism. In another embodiment, plunger rod 14 andstopper 16 may be co-formed such as by co-extrusion. In this manner,plunger rod 14 is locked to stopper 16, i.e., significant relativemovement between plunger rod 14 and stopper 16 is prevented and movementof plunger rod 14 can be transferred to stopper 16 to slide stopper 16between positions within syringe barrel 12. In other embodiments,plunger rod 14 and stopper 16 may be integrally formed as a plungerassembly.

All of the components of syringe assembly 10 may be constructed of anyknown material, and are desirably constructed of medical-grade polymers.

A stopper 16 of the present disclosure has structural features thatprovide a stopper having a higher resistance to leakage, reduced syringeforces such as pump and break-loose forces, and better demolding. Thisis achieved and maintained after sterilization and over the lifetime ofthe syringe, e.g., five (5) years.

Referring to FIGS. 2A and 2B, in one embodiment, a stopper 16 of thepresent disclosure includes a supported stopper design. For example,stopper 16 includes a first sealing rib 56A adjacent to a stopper roofportion 70A. In one embodiment, first sealing rib 56A of stopper 16 ispinched between the internal wall surface of barrel sidewall 30 and atip 68 of distal end 60 of plunger rod 14 as shown in FIG. 2B. In oneembodiment, a stopper 16 of the present disclosure is a supported 10 mlsyringe stopper design.

In other embodiments, a stopper 16 of the present disclosure includes anunsupported stopper design, e.g., the first sealing rib 56A of stopper16 is not pinched between the syringe barrel 12 and the plunger rod 14.

Referring to FIGS. 3-5, in one embodiment, stopper 16 includes an upperportion 50, a lower portion 52, and a middle portion 54 between upperportion 50 and lower portion 52. Stopper 16 includes a first sealing rib56 located adjacent to upper portion 50 and a second sealing rib 58located adjacent to lower portion 52. Stopper 16 also includes a roofportion 70 and a core portion 72 disposed adjacent to roof portion 70.The embodiment of stopper 16 shown in FIGS. 3-5 includes a shear element74 and a catch can element 76 which enable molding thermoplasticelastomer stoppers in open gate systems. In one embodiment, catch canelement 76 is configured to fit within the constraints of the otherfeatures of a molded part, such as enabling the shear element 74 andeasy part release. The volume of catch can element 76 may be variedbased on the attributes of a particular molding machine and toolingdesign. The catch can element 76 has a receiving volume that is at leastthe volume of the residual material left from a previous shot during amolding application.

Referring to FIGS. 4 and 5, first sealing rib 56A is sized and shaped toprovide an active sealing rib which results in a higher resistance toleakage. For example, referring to FIG. 2B, a stopper of the presentdisclosure includes a first sealing rib 56A which provides a firstcontact area 96 with the interior surface of sidewall 30 of syringebarrel 12, and a second sealing rib 58 which provides a second contactarea 98 with the interior surface of sidewall 30 of syringe barrel 12.

Referring to FIG. 15, the contact pressure of the stopper first sealingrib indicates the resistance to fluid leakage. A higher first sealingrib contact pressure leads to a higher resistance to leakage. In theactive sealing rib, i.e., first sealing rib 56, design of the presentdisclosure, as the fluid pressure increases, the contact pressure at thestopper sealing rib increases. Thus, a stopper of the present disclosureprovides a higher resistance to leakage. FIG. 15 illustrates the stopperof the present disclosure providing a higher resistance to leakage thana conventional stopper due to the above-described sealing rib design.

Referring to FIGS. 4 and 5, second sealing rib 58 includes a reducedthickness. In this manner, referring to FIG. 2B, the second contact area98, i.e., the contact area between second sealing rib 58 and theinterior surface of sidewall 30 of syringe barrel 12, is reduced. Such areduced second contact area 98 results in a reduction of syringe forcessuch as pump and break-loose forces.

Referring to FIGS. 4 and 5, roof portion 70 includes an increased roofthickness which results in improved leakage performance. For example,the increased roof thickness of stopper 16 of the present disclosureresults in a 20% increase in leakage pressure. The roof portion 70 ofstopper 16 helps contribute to the higher contact pressure uponapplication of fluid pressure which leads to a higher resistance toleakage as shown in FIG. 15.

Referring to FIGS. 4 and 5, core portion 72 includes a semi-ellipsoidalshape which results in better demolding of stopper 16. The angulardesign of core portion 72 prevents the rupture of the stopper andincreases mechanical strength of the core pin.

Referring to FIGS. 6-8, in another embodiment, a stopper 16B includes anupper portion 80, a lower portion 82, and a middle portion 84 betweenupper portion 80 and lower portion 82. Stopper 16B includes a firstsealing rib 86 located adjacent upper portion 80 and a second sealingrib 88 located adjacent lower portion 82. Stopper 16B also includes aroof portion 90 and a core portion 92. Stopper 16B can be moldable on avalve gate system.

Referring to FIG. 8, first sealing rib 86 is sized and shaped to providean active sealing rib which results in a higher resistance to leakage.For example, referring to FIG. 2B, a stopper of the present disclosureincludes a first sealing rib 86 which provides a first contact area 96Bwith the interior surface of sidewall 30 of syringe barrel 12, and asecond sealing rib 88 which provides a second contact area 98B with theinterior surface of sidewall 30 of syringe barrel 12.

As discussed above, the higher first sealing rib contact pressure of astopper of the present disclosure leads to a higher resistance toleakage. In the active sealing rib, i.e., first sealing rib 86, designof the present disclosure, as the fluid pressure increases, the contactpressure at the stopper sealing rib increases. Thus, a stopper of thepresent disclosure provides a higher resistance to leakage. FIG. 15illustrates the stopper of the present disclosure providing a higherresistance to leakage than a conventional stopper due to theabove-described sealing rib design.

Referring to FIG. 8, second sealing rib 88 includes a reduced thickness.In this manner, referring to FIG. 2B, the second contact area 98B, i.e.,the contact area between second sealing rib 88 and the interior surfaceof sidewall 30 of syringe barrel 12, is reduced. Such a reduced secondcontact area 98B results in a reduction of syringe forces such as pumpand breakloose forces.

Referring to FIG. 8, roof portion 90 includes an increased roofthickness which results in improved leakage performance. For example,stopper 16B of the present disclosure results in a 20% increase inleakage pressure. Referring to FIG. 8, core portion 92 includes arectangular shape. In other embodiments, it is contemplated that coreportion 92 may have other shapes. For example, core portion 92 may havean elliptical shape which helps in demolding during injection molding ofstoppers.

In one embodiment, stopper 16 of an exemplary embodiment is made of amaterial that provides the required functional properties of a stopperwithout requiring an external surface of the stopper to be lubricated.For example, stopper 16 may be formed of a thermoplastic elastomer. Inone embodiment, stopper 16 comprises a polyethylene based thermoplasticelastomer. In one embodiment, to reduce sticktion with syringe barrel 12of syringe assembly 10, stopper 16 comprises a polyethylene basedthermoplastic elastomer including at least 20% polyethylene withoptimized material properties, e.g., hardness, compression set, stress,and strain.

In one embodiment, e.g., a TPE-2 embodiment, stopper 16 may be formed ofa polyethylene blended with thermoplastic elastomer such as styreneblock copolymer. In another embodiment, stopper 16 may be formed of anolefin block copolymer based with polyethylene blocks. Such embodimentswith polyethylene or a similar structure such as but not limited toolefin block copolymer also reduce sticktion with syringe barrel 12 ofsyringe assembly 10.

Stopper 16 of the present disclosure provides a thermoplastic elastomerhaving reduced sticktion with a syringe barrel of a syringe assembly.Furthermore, stopper 16 of the present disclosure provides low syringeforces, such as breakloose force, breakout force, and sustaining force,and acceptable leak performance during shelf life, i.e., the durationbetween product manufacturing date and expiry date. Stopper 16 of thepresent disclosure provides such low syringe forces with low compressionset that stopper 16 does not require an external surface of the stopperto be lubricated.

In an exemplary embodiment of the present disclosure, the thermoplasticelastomer composition will include 30 to 65% by weight of thermoplasticelastomer, 10 to 35% by weight of polyolefin or other high meltingtemperature polymer, and 20 to 35% by weight of other additives such ashydrocarbon liquid, e.g., mineral oil. In other embodiments, the otheradditives may include other hydrophobic liquids with a high boilingtemperature to ensure that the required amount is present on and insidethe stopper. In other embodiments, the olefin block copolymer withpolyethylene hard phase (45 to 80%) may replace the thermoplasticelastomer and polyolefin or high melting temperature polymer.

Stopper 16 of the present disclosure does not require an externalsurface of the stopper to be lubricated due to the segregation of thehydrocarbon liquid such as mineral oil on the stopper surface. In thismanner, the stopper surface segregated hydrocarbon liquid acts as, andreplaces the need for, a lubricant and reduces the syringe operatingforces. The high hydrocarbon liquid surface segregation is determined bythe competition between energy and entropy of mixing. By having astopper of the present disclosure with higher viscosity or an increasein thermoplastic elastomer molecular weight, the extent of mixing of thehydrocarbon liquid in formulation decreases and a higher extent ofhydrocarbon liquid segregates to the stopper surface. In this manner,the surface segregated hydrocarbon liquid acts as, and replaces the needfor, a lubricant and reduces the syringe operating forces to the levelas observed with an externally lubricated stopper. Thus, a stopper ofthe present disclosure provides a stopper having the required functionalproperties of a stopper without requiring an external surface of thestopper to be lubricated, thereby eliminating the problems associatedwith applying a lubricant to a surface of a stopper. The problemsassociated with such a lubrication step include the required costs inlubricants and lubing instruments, the time and energy to operate andperform the lubrication step, and the requirement of the stopper needingto be removed from an automated assembly process to be lubricated. Astopper of the present disclosure, by eliminating the externallubrication step during assembly of a stopper, allows for completeautomation of a stopper during assembly.

In one embodiment, the presence of the polyethylene at the surface ofthe stopper combined with the surface energy of the stopper allows for astopper that has the required functional properties without requiring anexternal surface of the stopper to be lubricated, thereby eliminatingthe problems associated with applying a lubricant to a surface of astopper. For example, the lower surface energy of polyethylene (˜35mJ/m²) compared to polystyrene (˜41 mJ/m²) in a polyethylene andstyrenic block copolymer blend can result in preferential segregation ofpolyethylene to the surface, reduced interaction between stopper andbarrel material, and sticktion-free performance. In a TPE-2 embodiment,stopper 16 may be formed of a polyethylene blended with styrene blockcopolymer. Since the hard phase of styrenic block copolymer ischemically linked to the soft phase, the polyethylene is preferentiallysegregated to the surface. Polypropylene is not as desired as polyolefinfor a stopper application in a syringe with a polypropylene orpolypropylene copolymer barrel because of the increased interactionbetween the polypropylene in the stopper and the barrel which may resultin sticktion.

Furthermore, providing a stopper having increased thermoplasticelastomer molecular weight to achieve the viscosity requirements, alsosolves the high compression set problem encountered with many previousstoppers for syringe assembly application. The addition of a lowviscosity hydrocarbon liquid, such as mineral oil, to the stopper of thepresent disclosure also improves the flow characteristics of thecomposition of the stopper blend at the thermoplastic elastomerprocessing temperature. In one embodiment, the thermal expansioncoefficient of a syringe stopper can be reduced by the addition of aninorganic filler such as silica or calcium carbonate due to the lowthermal expansion coefficient of such inorganic fillers and theirinfluence on the crystalline architecture of the TPE matrix. In thismanner, the addition of an inorganic filler compensates for the highcoefficient of thermal expansion of a thermoplastic elastomer.

As described above, stopper 16 may be formed of a non-lubricatedthermoplastic elastomer. Such a stopper 16 provides for a lowcompression set. For example, a non-lubricated thermoplastic elastomerstopper 16 provides a compression set equal to or lower than 35% at 25%compression for 22 hours and 70 degrees C. A stopper of the presentdisclosure provides the required compression set through the use of highmolecular weight components.

In one embodiment of the present disclosure, a stopper for a syringeassembly includes a thermoplastic elastomer, wherein the compression setof the thermoplastic elastomer is ≤50% when measured at 25% compressionfor 22 hrs at 70 degrees C. In another embodiment, the compression setof the thermoplastic elastomer is approximately ≤35% when measured at25% compression for 22 hrs at 70 degrees C. In another embodiment, thecompression set of the thermoplastic elastomer is approximately 10%-35%when measured at 25% compression for 22 hrs at 70 degrees C.

A low compression set is desired for a syringe stopper application asthe interference of a stopper with a barrel dictates both syringe useforces and leak performance. In the case of a high compression set, thesyringe leak and force performance would be fine after assembly but theleak performance would suffer during the syringe shelf life as shown inFIG. 20. FIG. 20 illustrates that a TPE stopper material with acompression set level above 50% (ASTM D395-03, Method B, 22 hrs at 70°C.) has poor leakage performance during syringe shelf life.

Furthermore, stopper 16 of the present disclosure provides a better handfeel of syringes with a plurality of different fluids. For example, thehand control of filling a syringe with a fluid without a needle attachedis improved and the use of stopper 16 of the present disclosure with asyringe assembly provides good control at the droplet level, e.g.,placing a droplet of blood on a slide for evaluation. By improving thehand control of a syringe assembly, a clinician is able to smoothlydeliver a fluid to a patient thereby reducing any patient discomfort.Furthermore, by improving the hand control of a syringe assembly, anysquirt of a fluid leading to contamination is eliminated. A stopper ofthe present disclosure provides the improved hand control propertiesthrough the use of high molecular weight components. Additionally, astopper of the present disclosure utilizes the higher viscosity of TPEto provide a stopper that provides the above-described functionalperformance factors for a syringe assembly while eliminating theexternal lubricant on a stopper. For example, stoppers formed of a lowerviscosity than the TPE-2 embodiment of the present disclosure may havebad control with spurting with isopropanol and blood. Thus, the higherviscosity of the TPE-2 embodiment of the present disclosure is animportant factor for the good hand control factors.

Referring to FIG. 14B, a table is provided showing the improved handcontrol properties of a stopper of the present disclosure formed of anOlefin block copolymer, e.g., a TPE-1 embodiment, and of a stopper ofthe present disclosure formed of a polyethylene blended with styrenicblock copolymer, e.g., a TPE-2 embodiment. The TPE-4 embodiment, whichis a polypropylene blended with styrene block copolymer formulation withlower viscosity than TPE-1 and TPE-2 embodiments, exhibits bad liquidcontrol with spurting (FIG. 14A). The TPE-5 embodiment, which is alsobased on polyethylene blended with styrene block copolymer, similar toTPE-2 but of lower viscosity (such as shown in FIG. 14A), also exhibitpoor liquid control with spurting. A minimum viscosity of the TPEformulation, as documented for the embodiments in this disclosure, isrequired for good hand control of stopper formulations when used insyringe applications.

With reference to FIG. 14B, a stopper of the present disclosure isformed of a TPE with a high viscosity that provides additionaladvantages such as no external lubricant on the stopper and improvedhand control over conventional stoppers. A stopper of the presentdisclosure provides for improved and/or preferred maintenance of thehand control of the syringe with fluids, and/or limited excipientinteractions. A stopper of the present disclosure formed of a highviscosity TPE helps in achieving better hand control with differentfluids. A stopper of the present disclosure formed of a high viscosityTPE provides for improved and/or preferred excipient interaction or handcontrol of syringe with fluids. Different hand control of fluids can beobserved such as good control at droplet level (best control), goodcontrol but stream of fluid instead of droplet comes out on the start ofplunger motion, good control with droplet level at start but spurtingduring the middle of fluid injection, starts with spurt but controlimproves later, and starts with spurt and no control during fluidinjection or bad control with spurting (worst control).

Slip additives are commonly added in the TPE formulation to decrease thecoefficient of friction. An unexpected effect was observed on syringehand control by the presence of a slip additive in TPE stopperformulation (along with the impact of formulation viscosity on thisperformance as shown in FIG. 14A). By adding a slip additive, such asbut not limited to Erucamide, Oleamide, or Behenamide at concentrationsless than 1%, the hand control significantly improves above a criticalconcentration of slip additive as shown in FIG. 26. The presence of aslip additive in TPE stopper formulation also impacts syringe forces, asexpected by the decrease in friction coefficient as shown in FIG. 22.

Referring to FIG. 21, a stopper of the present disclosure is formed of ahigh viscosity TPE. Viscosity below a critical level leads to poorexcipient hand control with spurting of fluid during injection. In oneembodiment of the present disclosure, the viscosity of the thermoplasticelastomer is ≥70.0 Pa·s at 1,000 s⁻¹ shear rate, ≥12.0 Pa·s at 10,000s⁻¹ shear rate, and ≥3.0 Pa·s at 50,000 s⁻¹ shear rate when measuredusing a capillary rheometer at 205 degrees C. (Die: Roundhole 20 mmlength/1 mm diameter/180 degree inlet, Piston: d=15 mm, and meltingtime=7 min). In one embodiment, the viscosity of the thermoplasticelastomer is from 70.0 Pa·s to 320.0 Pa·s at 1,000 s⁻¹ shear rate. Inanother embodiment, the viscosity of the thermoplastic elastomer is from100.0 Pa·s to 170.0 Pa·s at 1,000 s⁻¹ shear rate. In another embodiment,the viscosity of the thermoplastic elastomer is from 12.0 Pa·s to 46.0Pa·s at 10,000 s⁻¹ shear rate. In another embodiment, the viscosity ofthe thermoplastic elastomer is from 16.0 Pa·s to 27.0 Pa·s at 10,000 s⁻¹shear rate. In another embodiment, the viscosity of the thermoplasticelastomer is from 3.0 Pa·s to 12.0 Pa·s at 50,000 s⁻¹ shear rate. In oneembodiment, the viscosity of the thermoplastic elastomer is from 4.5Pa·s to 7.5 Pa·s at 50,000 s⁻¹ shear rate.

A stress-strain curve is a material property that characterizes thebehavior of a particular material. The linear portion of thestress-strain curve is governed by a relationship known as Hooke's Law.For a stopper, this stress-strain relationship is converted into anappropriate material model that acts as one of the inputs to FEA duringthe design process.

In one embodiment, the stress at desired strain values is also optimizedfor the thermoplastic elastomer stopper of the present disclosure so asto obtain good leak and force performance with an assembled syringe.Referring to FIG. 11, a table with the desired stress values isprovided.

Referring to FIGS. 11-14B, in one embodiment, e.g., a TPE-1 embodiment,stopper 16 may be formed of an olefin block copolymer. In anotherembodiment, e.g., a TPE-2, TPE-3 or TPE-5 embodiment, stopper 16 may beformed of a polyethylene blended with styrenic block copolymer. Inanother embodiment, e.g., a TPE-4 embodiment, stopper 16 may be formedof a polypropylene blended with styrenic block copolymer. Conventionalbased stoppers may be formed of a styrenic based or polyisoprene basedmaterial.

The present disclosure provides for a thermoplastic elastomer stopperthat meets the desired material properties and design of a stopper for asyringe assembly. Referring to FIGS. 12 and 13, tables are provideddemonstrating the importance of the design and the desired physicalproperties for the material of a stopper of the present disclosure. Itis noted herein that test method “IT” shown in FIG. 12 adheres to ISOstandard 7886-1:1993. In one embodiment, the material properties mayinclude compression set, hardness, stress at given strain levels, andviscosity at given shear rates. In one embodiment, the compression setof a thermoplastic elastomer stopper of the present disclosure may be≤50% when measured at 25% compression for 22 hrs at 70 degrees C. (ASTMD395-03, Method B). In one embodiment, the hardness of a thermoplasticelastomer stopper of the present disclosure should be in the range of40-70 Shore A (ASTM D2240-05). The stress at desired strain valuesshould also be optimized for the thermoplastic elastomer stopper of thepresent disclosure so as to obtain good leak and force performance withthe assembled syringe. In one embodiment, the viscosity of athermoplastic elastomer stopper of the present disclosure may be ≥70.0Pa·s at 1,000 s⁻¹ shear rate, ≥12.0 Pa·s at 10,000 s⁻¹ shear rate, and≥3.0 Pa·s at 50,000 s⁻¹ shear rate. In one embodiment, a thermoplasticelastomer stopper of the present disclosure provides for sticktion-freeperformance with a polypropylene or polypropylene copolymer basedbarrel. For example, a stopper of the present disclosure includes a30-65% thermoplastic elastomer such as but not limited to 30-65%styrene-ethylene-butylene-styrene (SEBS) copolymer blended with 10-35%polyolefin or higher melting temperature polymer such as but not limitedto 10-35% medium to high density polyethylene (medium to high densitywith melting temperature of from 120 degrees C. to 130 degrees C.) butexcluding polypropylene, 20-35% commonly available mineral oil alongwith commonly available radiation stabilizer, antioxidant, and/orprocessing aids. The molecular weight of the SEBS and polyethylene areselected so as to obtain the desired material properties as describedabove.

The important characteristics of the materials used to make stopper 16is that stopper 16 is made of a material that along with design for lowforces provides the required functional properties of a stopper withoutrequiring an external surface of the stopper to be lubricated. Stopper16 of an exemplary embodiment may have the following materialproperties. In one embodiment, it is contemplated that stopper 16 has astopper material hardness of approximately 45 Shore A Hardness toapproximately 65 Shore A Hardness. In some embodiments, it iscontemplated that stopper 16 has a stopper material hardness ofapproximately 53 Shore A Hardness to approximately 63 Shore A Hardness.

The present disclosure provides for a thermoplastic elastomer stopperthat meets the desired material properties of a stopper for a syringeassembly. These material properties include hardness and compressionset. These properties along with findings that no more than a criticaldefined concentration of barrel material in the stopper formulation andhigh viscosity resin used in the stopper formulation results in stoppersof improved performance, e.g., better syringe control during handinjection and pump use. The desired range for hardness of a stopper ofthe present disclosure is reflected by the desired stress values atgiven strain levels as shown in FIG. 11. A syringe stopper has twocompeting requirements, good leakage performance and low operatingforces, and they are met by a stopper material of a required hardness. Astopper material of a low hardness would have poor leak performance anda stopper material of a high hardness would have a high (undesired)force performance resulting in a leakage of the fluid in the barrel pastthe stopper ribs.

A stopper of the present disclosure also provides a sticktion-freesyringe stopper manufactured from the composition of the presentdisclosure. An autoclavable syringe can be obtained with the use of highmelting temperature polymer in formulation.

Conventional autoclavable stoppers generally are formed of thermosetrubbers coated with a lubricant. However, manufacturing of suchconventional autoclavable stoppers requires multiple processing stepsand generates increased excess waste.

Conventionally, a thermoplastic elastomer stopper based on polypropyleneblends can also be used in autoclavable syringes. The autoclavablitiy ofsuch syringes is obtained by the addition of a lot of inorganic fillersinto a stopper formulation to provide structural integrity atautoclaving temperatures. The use of inorganic fillers damages thesurface of the mold resulting in reduced efficiency and high runningcosts. Also, the presence of inorganic fillers in the compositionresults in issues associated with extractables and leachables during useand storage of syringes. Therefore, there is a need for a thermoplasticelastomeric composition for the manufacturing of syringe stoppers whichcan be autoclaved without the need for inorganic fillers.

As discussed above, a stopper of the present disclosure is made of amaterial that provides the required functional properties of a stopperwithout requiring an external surface of the stopper to be lubricated.For example, a stopper of the present disclosure may be formed of athermoplastic elastomer. In this manner, a stopper of the presentdisclosure also allows for an autoclavable stopper for a syringeassembly.

In one embodiment, the thermoplastic elastomer composition of a stopperof the present disclosure is based on high melting temperature polymers.For example, a melting temperature ≥170 degrees C. is required forautoclavable syringes.

As previously discussed, in one embodiment, a stopper of the presentdisclosure may be formed of a thermoplastic elastomer compositionincluding a blend of injection moldable elastomers including blockcopolymers and a high transition temperature polymer. In someembodiments, the elastomer may include a styrene block copolymer, anolefin block copolymer, polyisoprene, and butyl rubber blended with thehigh transition temperature polymers which may includeethylene-tetrafluoro-ethylene (ETFE) and fluorinated ethylene propylene(FEP) polymers.

In one embodiment, the composition of a stopper of the presentdisclosure may include 30 to 65% by weight of elastomers such as but notlimited to styrene block copolymer and olefin block copolymer, 10 to 35%by weight of high transition temperature polymers such as but notlimited to ethylene-tetrafluoro-ethylene, and 20-35% by weight of otheradditives such as mineral oil to meet the desired processingrequirements and material properties such as hardness, tensile,viscosity, and compression set properties for a stopper for a syringeassembly application. In other embodiments, the composition of a stopperof the present disclosure contains a radiation stabilizer, anantioxidant, and/or a processing aid.

A stopper of the present disclosure overcomes the deficiencies ofconventional stoppers by providing an injection moldable thermoplasticsyringe stopper wherein the sticktion free performance is generated bythe migration to the surface of hydrocarbon liquids such as mineral oilincorporated in the composition of the stopper. The high temperaturestable polymer at the level of at least 10 to 35% by weight in thecomposition provides structural integrity during autoclaving processesand any other exposure to high temperature conditions. For example, thehigh transition temperature polymers may includeethylene-tetrafluoro-ethylene (ETFE) and fluorinated ethylene propylene(FEP) polymers. As discussed above, the thermoplastic elastomercomposition of a stopper of the present disclosure is based on highmelting temperature polymers. For example, a melting temperature ≥170degrees C. is required for autoclavable syringes. In this manner, astopper of the present disclosure results in a lubricant free,sticktionless, autoclavable, and injection moldable stopper whileeliminating the step of an external lubrication on a stopper.

A stopper of the present disclosure also provides additional advantagesrelating to manufacturing and/or molding. For example, in oneembodiment, a stopper of the present disclosure includes ashear-feature, i.e., a thin-wall section, at the mold gating pointwithin a mold cavity. The shear-feature of a stopper of the presentdisclosure adds shear heat at the mold gate point. In this manner, astopper of the present disclosure eliminates cold material from enteringthe mold cavity, eliminates flow lines and/or weld lines common tostopper molding, eliminates sink marks, improves the control of gatequality, improves the mold cycle time, and eliminates surface and/orvisual imperfections.

As described above, the embodiment of stopper 16 shown in FIGS. 3-5includes shear element 74 and catch can element 76 which enable moldingthermoplastic elastomer stoppers in open gate systems. Open gate systemscan also be referred to as hot tip systems. In one embodiment, shearelement 74 has a thickness that is less than 52% and greater than 36% ofthe thickness of roof portion 70 of stopper 16. In one embodiment, shearelement 74 has a thickness that is approximately 44% of the thickness ofroof portion 70 of stopper 16. In one embodiment, shear element 74 isapproximately 50% of the general wall thickness at the gate location. Inone embodiment, shear element 74 has a thickness of 0.012 inches. In oneembodiment, shear element 74 has a thickness of 0.018 inches. In oneembodiment, shear element 74 has a thickness of 0.023 inches.

In a conventional open gate hot runner system, the gate cannot close offcausing residual heat and pressure which results in a small amount ofunmelted and/or slightly melted residual resin left from the previousshot. This material then gets pushed in and incorporated into thestopper, or other molded part, during the next shot. Furthermore, thisresidual material can go anywhere within the molded part. If theresidual material lands on the surface of the stopper it will compromisethe aesthetic quality of the part and depending on the location couldcause functional performance issues. For example, if the residual unmeltlands on the surface of the stopper rib it will impede the stopper fromsealing to the barrel wall and result in leakage and a product failure.This residual material compromises the quality and performance of themolded part, increasing scrap rate and thus resulting increased cost.

Referring to FIGS. 4 and 5, catch can element 76 is designed to enableeasy part release. Catch can element 76 is designed to fit within theconstraints of other features of the molded part, to enable the shearfeature and optimize easy part release. Catch can element 76 is alsodesigned to fit within the constraints of the other features of themolded part, such as enabling shear element 74. Catch can element 76includes a receiving volume which is dependent on attributes of themolding machine and tooling design. In one embodiment, catch can element76 has a volume that is at least the volume of the residual materialleft from the previous shot. In one embodiment, catch can element 76needs to be of a sufficient volume that is dictated by the hot runnerdrop and located opposite the gate.

Referring to FIG. 27, the catch can element 76 and a hot-tip portion 200of a hot runner system is illustrated. In one embodiment, a gate portion204 adjacent the stopper 16 is capable of slowly moving into the catchcan element 76. In this manner, the residual material can be trappedwithin the catch can element 76 so that it will not flow into themolding area of the stopper 16 causing flow lines and/or knit lines inportions of the stopper 16.

Referring to FIG. 28, a cold slug 210 of TPE sets up at the end of thehot tip 212 at the end of the molding cycle that is then injected intothe cavity the following cycle. This cold material does not re-melt backinto the flow path of the new material and can become lodged in asealing rib of the stopper 16, causing a leakage path. The catch canelement 76 needs to be of a sufficient size to capture the cold slug 210and the shear element 74 gap needs to be small enough to keep the coldslug 210 from passing through with the good TPE, similar to a strainer.The geometry of the catch can element 76 and the shear element 74 aregoverned by the size of the gate slug that is produced by the hot-tiphot runner system, not the size of the stopper being molded.

Referring to FIG. 5, core portion 72 includes a shape which results inbetter demolding of stopper 16. The angular position of core portion 72prevents rupture of the stopper and improves mechanical strength of thecore pin.

Referring to FIG. 2B, core portion 72 includes a semi-ellipsoidal shape79 that has a radius that helps in distributing the plastic in cavity.The semi-ellipsoidal shape 79 also adds strength to the stopper 16 andimproves the ejection of the center of the stopper 16.

Referring to FIGS. 3 and 6, a stopper of the present disclosure alsoincludes umbrella arm elements 78, 94. Umbrella arm elements 78, 94enable a fully supported stopper roof with the plunger rod withoutrequiring full contact across the whole under stopper surface area.Umbrella arm elements 78, 94 decrease cycle time and reduce the amountof resin used per shot. In this manner, umbrella arm elements 78, 94provide a cost savings in production output and in raw material. Also,umbrella arm elements 78, 94 provide an environmentally green advantageby providing a system that requires less raw material.

As previously discussed, the problems of excessive breakout andbreakloose forces are related to friction. Friction is generally definedas the resisting force that arises when a surface of one substanceslides, or tends to slide, over an adjoining surface of itself oranother substance. Between surfaces of solids in contact, there may betwo kinds of friction: (1) the resistance opposing the force required tostart to move one surface over another, conventionally known as staticfriction, and (2) the resistance opposing the force required to move onesurface over another at a variable, fixed, or predetermined speed,conventionally known as kinetic friction.

The force required to overcome static friction and induce breakout isreferred to as the “breakout force”, and the force required to maintainsteady slide of one surface over another after breakout or breakloose isreferred to as the “sustaining force”. Two main factors contribute tostatic friction and thus to the breakout or breakloose force. The term“stick” as used herein denotes the tendency of two surfaces instationary contact to develop a degree of adherence to each other. Theterm “inertia” is conventionally defined as the indisposition to motionwhich must be overcome to set a mass in motion. In the context of thepresent invention, inertia is understood to denote that component of thebreakout force which does not involve adherence.

Breakout or breakloose forces, in particular the degree of stick, varyaccording to the composition of the surfaces. In general, materialshaving elasticity show greater stick than non-elastic materials,particularly when the surfaces are of similar composition. The length oftime that surfaces have been in stationary contact with each other alsoinfluences breakout and/or breakloose forces. In the syringe art, theterm “parking” denotes storage time, shelf time, or the interval betweenfilling and discharge. Parking generally increases breakout orbreakloose force, particularly if the syringe has been refrigeratedduring parking.

As discussed, conventional stoppers require the application of alubricant to a surface of a stopper. The present disclosure provides astopper that is made of a material that provides the required functionalproperties of a stopper without requiring an external surface of thestopper to be lubricated.

Referring to FIG. 9, a thermoplastic elastomer stopper based on astyrene block copolymer blended with polypropylene in combination with apolypropylene barrel exhibits sticktion, i.e., in a stationary position,the stopper develops a degree of adherence to the interior surface of asyringe barrel and requires a breakloose force to overcome the frictionbetween the stopper and the interior surface of the polypropylenesyringe barrel. The sticktion between the stopper and the syringe barrelmakes it difficult to provide smooth incremental line-to-lineadvancement of the stopper within the syringe barrel.

Referring to FIG. 10, a stopper of the present disclosure based on astyrene block copolymer blended with polyethylene, which does notrequire an external surface of the stopper to be lubricated due to thesegregation of the hydrocarbon liquid such as mineral oil on the stoppersurface, does not exhibit sticktion and provides the smooth incrementalline-to-line advancement of the stopper within the syringe barrel. Thisallows for a fluid to be dispensed from a syringe assembly in accuratelycontrolled quantities. In other embodiments, a stopper of the presentdisclosure formed of an olefin block copolymer exhibits thesticktion-free performance, similar to as shown in FIG. 10.

In one embodiment, syringe barrel 12 is formed of a first material andstopper 16 is formed of a second material different than the firstmaterial, wherein the second material does not contain more than 4% ofthe first material and more preferably the second material does notcontain more than 1.5% of the first material and still more preferablythe second material does not contain more than 1% of the first material.For example, stopper 16 may be formed of a polyethylene basedthermoplastic elastomer and syringe barrel 12 may be formed of apolypropylene. In other embodiments, stopper 16 may be formed of apolyisoprene or SBR material and syringe barrel 12 may be formed of aglass, cycloaliphatic polyolefins, polyesters, or polycarbonatematerial. In this manner, the degree of adherence that the stopperdevelops to the interior surface of a syringe barrel is reduced, e.g.,the chemical interaction between the stopper and the syringe barrel ismitigated, and the stopper and the syringe barrel do not exhibitsticktion and the syringe assembly provides smooth incrementalline-to-line advancement of the stopper within the syringe barrel. Thisallows for a fluid to be dispensed from a syringe assembly in accuratelycontrolled quantities.

The tests, research, and experimentation of the present disclosure wereconducted for stopper stick-slip motion at a low speed (0.1 ml/hr with10 ml syringe configuration) with polypropylene (PP) barrel and PPcontent in a TPE stopper as shown in FIG. 17. Smooth stopper motion isdesired for continuous drug delivery at low rates. As can be observed inFIG. 17, at PP concentrations of 1% and lower, there is no stick-slipstopper motion. In contrast, the stick-slip motion occurrences increasesabove this critical PP concentration and is exhibited by all syringes atPP concentrations of 5.7% and higher. These results would translatesimilarly to a barrel of an alternate resin composition and that sameresin being incorporated into the stopper formulation.

The composition of the thermoplastic stopper resin should not have thesame material as in the barrel so as to avoid sticktion. For examplewith a polypropylene or polypropylene copolymer based barrel, thestopper formulation should not be polypropylene based. A thermoplasticelastomer with formulation based on lower surface tension hard phasealso helps in reducing sticktion. For example, styrenic block copolymer(polystyrene surface tension ˜41 mN/m) mixed with polyethylene (surfacetension ˜35 mJ/m²) or ETFE (˜23 mN/m²) results in preferential surfacesegregation of hard phase and reduced interaction with the barrel.

In syringe assemblies including a stopper and a syringe barrel formed ofthe same material, the chemical interaction between the stopper and thesyringe barrel is increased and it results in sticktion between thestopper and the syringe barrel. For example, during the stationaryposition, the stopper develops a degree of adherence to the innersurface of the barrel and requires a breakloose force (typically higherthan the sustaining force) which is the force required to overcome thestatic friction between the surfaces of the stopper and the syringebarrel. In extreme cases, adhesion between the barrel and stopper candevelop at slower motions making it difficult to provide smoothincremental line-to-line advancement of the stopper within the syringebarrel. In the case of pump application syringes with such a stopper,the drug delivery would not be smooth and thus is not desirable. Forpolypropylene (PP) based barrels, the stopper should not have above acritical level of PP in its formulation, as shown in FIG. 17, for smoothor no stick-slip motion during pump usage (pump speed of 0.1 ml/hr using10 ml syringe). The PP content in these formulations was calculatedusing energy of melting from DSC corresponding to PP, energy of meltingof 100% crystalline PP as 293 J/g, and assuming 50% PP crystallinity instopper material. The DSC peak associated with PP melting was notidentifiable in TPE-1, TPE-2 (all slip agent levels), TPE-3, TPE-5, andTPE-6 indicating that the PP content in these TPE is <1%. FIG. 17indicates that formulations TPE-4, TPE-10, TPE-11, TPE-12, TPE-13,TPE-14, and TPE-15 have PP content >1% and fails the stick-slipperformance requirement. An example of a syringe pump force profile forTPE-2-S0.6 and TPE-4 (silicone lubricant lubed) are shown in FIGS. 9 and10. Even though TPE-6 has a PP content <1%, TPE-6 fails to meet the nosticktion performance. This is due to the minimum amount of polyethylenerequired in a styrenic block copolymer stopper system.

Based on the research and experimentation of the present disclosure, ifthe syringe barrel 12 is formed of a first material and the stopper 16is formed of a second material different than the first material,wherein the second material does not contain more than 4% of the firstmaterial and more preferably the second material does not contain morethan 1.5% of the first material and still more preferably the secondmaterial does not contain more than 1% of the first material, then thestick-slip motion of the stopper against the plunger rod is avoided. Forexample, as described above, stopper 16 may be formed of a polyethylenebased thermoplastic elastomer and syringe barrel 12 may be formed of apolypropylene. In other embodiments, stopper 16 may be formed of apolyisoprene or SBR material and syringe barrel 12 may be formed of aglass, cycloaliphatic polyolefins, polyesters, or polycarbonatematerial. In this manner, as described above, the degree of adherencethat the stopper develops to the interior surface of a syringe barrel isreduced, e.g., the chemical interaction between the stopper and thesyringe barrel is mitigated, and the stopper and the syringe barrel donot exhibit sticktion and the syringe assembly provides smoothincremental line-to-line advancement of the stopper within the syringebarrel. This allows for a fluid to be dispensed from a syringe assemblyin accurately controlled quantities.

Breakout or breakloose forces, in particular the degree of stick, varyaccording to the composition of the surfaces. In general, materialshaving elasticity show greater stick than non-elastic materials,particularly when the surfaces are of similar composition. The length oftime that surfaces have been in stationary contact with each other alsoinfluences breakout and/or breakloose forces. In the syringe art, theterm “parking” denotes storage time, shelf time, or the interval betweenfilling and discharge. Parking generally increases breakout orbreakloose force, particularly if the syringe has been refrigeratedduring parking.

As is known in the art, conventional stoppers require the application ofa lubricant to a surface of a stopper. The present disclosure provides astopper that is made of a material that provides the required functionalproperties of a stopper without requiring an external surface of thestopper to be lubricated. A stopper of the present disclosure includes astopper material having a high enough viscosity which is made possibleby a high molecular weight of the elastomer and/or a hard phase of theformulation. The mineral oil incorporated in the formulation segregatesto the stopper surface due to a low entropy of mixing and satisfies therole played by externally applied silicone lubricant on a conventionalsyringe stopper surface.

FIG. 13 documents the hand forces for lubed and unlubed TPE stoppers ina 10 ml embodiment after gamma sterilization. The syringe hand forcesare similar for syringes with lubed and unlubed stoppers.

In one embodiment, a stopper of the present disclosure is formed of aTPE based on a polyethylene blended with styrenic block copolymer. Insuch an embodiment, the propensity of the polyethylene to the surface ofthe stopper and the surface energy of the stopper enables anon-lubricated stopper that has the required functional properties of astopper without requiring an external surface of the stopper to belubricated, thereby eliminating an extra step of lubricant applicationonto syringe stopper surface. In this manner, the negative consequencesof the external lubricant application on a stopper are eliminated. Forexample, the lubrication step on a stopper requires cost in lubricantsand lubing instruments, time, and energy to operate and perform thelubrication step, and the stopper must be removed from an automatedassembly process to be assembled. The non-lubricated stopper of thepresent disclosure also provides a stopper which allows for a completeautomation stopper assembly process. The lower surface energy ofpolyethylene (˜35 mJ/m²) compared to polystyrene (˜41 mJ/m²) in apolyethylene and styrenic block copolymer blend can result intopreferential segregation of polyethylene to the surface, reducedinteraction between stopper and barrel material, and sticktion-freeperformance. This is also supported by an Atomic Force Microscopy (AFM)measurement on a TPE-2-S0.6 embodiment, where hard phase ispreferentially segregated towards the surface. Since the hard phase ofstyrenic block copolymer is chemically linked to the soft phase, thissuggests that polyethylene is preferentially segregated to the surface.To determine the critical concentration of polyethylene needed in astyrenic block copolymer, two TPE stopper formulations with polyethylenecontent of 8% (TPE-6) and 25% (TPE-2 with all slip agent level andTPE-5) were studied in a 10 ml embodiment with a polypropylene barreland plunger rod. For example, the pump force profile for TPE-2-S0.6 andTPE-6 are given in FIGS. 18 and 19. Sticktion at 0.1 ml/hr pump speedwas observed with the formulation with 8% polyethylene content but nosticktion in case of 25% polyethylene content, indicating that thecritical polyethylene concentration exists in the 8% to 25% range.

The syringe stopper is constantly under stress in the syringe assemblyand undergoes a compression set with time. Syringe functionalperformances, hand force and leak performance, are dependent on stopperdimension and are competing requirements. Syringe hand forces increaseor become worse and pressure to leak increases or becomes better with anincrease in stopper OD. Since a stopper OD is the highest just afterassembly, the hand force is a worst case for just assembled syringes. Incontrast, pressure to leak decreases or becomes worse with time. In oneembodiment, the stopper design and dimensions are designed to achieveacceptable hand forces at T=0 but at the same time satisfy leakperformance during the entire shelf life. A compression set measurement(ASTM D395-03, Method B, 25% strain for 22 hrs at 70 degrees C.) gives agood indication of the magnitude of stopper OD change with time. Theleak performance for different TPE stopper embodiments, as shown in FIG.20, suggests that the leakage performance was not met by the TPEformulations with compression set >50%. The formulations with acceptableleakage performance had a compression set ≤35%.

As discussed above, unlubed stoppers having a high TPE viscosity is notonly helpful in the ability to have unlubed stoppers but also providesgood control in the ability to dispense filled liquid from a syringe.The ability to dispense droplets of blood without any squirting orjetting is important for the use of a syringe in applications whereblood droplets are placed on glass slides for analysis. Jetting of bloodwould result in the contamination of a work place during such practiceand the possibility of infection to health care workers, which is notdesirable. Additionally, such syringes can dispense small highlyaccurate increments of liquid repeatedly without sudden surges. Thus, asyringe assembly including a stopper of the present disclosure can beused to administer a medicament to a patient without the danger ofsurges whereby accurate control of dosage and greatly enhanced patientsafety are realized.

Attaching a needle to a syringe creates back-pressure and improves thehand control. Thus, all of the tests, research, and experimentation ofthe present disclosure were conducted in the worst case of syringeswithout an attached needle. The test for the ability to control blooddispensing at droplet level was conducted in 10 ml and E-beam sterilizedsyringes using sheep blood as shown in FIG. 21. FIG. 21 also documentsthe viscosity at different shear rates measured using a capillaryrheometer at 205° C. (Die: Roundhole 20 mm length/1 mm diameter/180degree inlet, Piston: d=15 mm, and melting time=7 min). TPE-1-S0.6 andTPE-2 (with all slip agent level), with high formulation viscosity,exhibit good hand control but low viscosity. TPE-3 (polypropyleneblended with styrenic block copolymer based) and TPE-5 (polyethyleneblended with styrenic block copolymer) exhibit poor hand control withblood.

The amount of slip agent (such as but not limited to Erucamide,oleamide, and behenamide) present in the TPE formulation also impactssyringe hand control with different fill liquids. For example, thetests, research, and experimentation of the present disclosure includehand control tests for isopropanol dispensed at droplet level forpolyethylene blended with styrenic block copolymer based TPE-2 withdifferent levels of slip agent, Erucamide, in a 10 ml stopper(Design-5). A critical level of slip agent between 0.2-0.3% is neededfor good syringe hand control. In the case of such formulation, stopperstrain in assembled syringes should be optimized to eliminate any visualdefect due to the preferential segregation of slip agent on the stoppersurface. Such visual defect can give the perception of foreign matter tothe end user. The presence of a slip agent in the formulation alsodecreases or improves the syringe forces without impacting the leakperformance as syringe leak performance is primarily dependent on theinterference between syringe components. FIG. 22 documents the forcechanges with different slip agent level TPE-2 stoppers in 10 ml Design-5and E-beam sterilized syringes.

The TPE stopper in a syringe assembly undergoes complex compression andtensile modes during use and the TPE material property in both tensileand compression affects the syringe functional performance (hand forceand leak performance). A stress-strain curve is a material property thatcharacterizes the behavior of a particular material. The tests,research, and experimentation of the present disclosure include usingFEA simulation to predict the desired stress at a given strain levelthat would result in the best functional performance. Referring to FIG.11, the stress values for a desired curve for TPE-1-S0.6, TPE-2-S0.6,and TPE-3 are given. The tests, research, and experimentation of thepresent disclosure include using FEA simulation to assign relativeranking for syringe leakage pressure and sustaining force for thesethree TPE formulations (FIG. 23) and it matched with the experimentaldata (FIG. 24). The leak pressure and sustaining force test wasconducted in 10 ml Design-4 in non-sterile condition (aged for 1 week at60° C.). TPE-3 had the lowest or worst leak performance. Even though thesustaining force with TPE-1-S0.6 and TPE-2-S0.6 were higher than TPE-3,it was acceptable. Since leak performance becomes worse with time,TPE-1-S0.6, TPE-2-S0.3, and TPE-2-S0.6 can be selected as the final TPEformulation with no sticktion and acceptable syringe force and leakperformance with the possibility to be used without externally appliedsilicone lube.

TPE stress at a given strain is also reflected by the hardness of theformulation. TPE1-S0.6 and TPE-2 (with 0.3% and 0.6% Erucamide level),which meet the stress at given strain requirement, have a hardness of 53Shore A and 63 Shore A. Thus, the most preferred hardness range for aTPE stopper formulation of the present disclosure is 53-63 Shore A.

Based on the above presented data, the final TPE selection table for asyringe stopper is presented in FIG. 25. TPE-1-S0.6, TPE-2-S0.3, andTPE-2-S0.6 meet all the requirements for a syringe stopper applicationand can be used in an unlubed condition.

In the case of using a syringe with TPE stopper of a higher thermalexpansion coefficient than the barrel material, accidental exposure athigh temperatures (such as 60° C.) for prolonged time leads to barrelbulge. This is due to the increased stress on the barrel at hightemperature due to the mismatch in thermal expansion coefficient leadingto non-reversible creep of the barrel or bulging at a stopper parkingposition. The thermal expansion coefficient of a syringe stopper can bereduced by the addition of an inorganic filler such as silica or calciumcarbonate due to the low thermal expansion coefficient of such inorganicfillers and their influence on the crystalline architecture of the TPEmatrix. In this manner, the addition of inorganic filler compensates forthe high coefficient of thermal expansion of a thermoplastic elastomerresulting into an acceptable creep level of barrel material.

An autoclavable syringe can also be obtained with the use of a highmelting temperature polymer in formulation. Conventional autoclavablestoppers generally are formed of thermoset rubbers coated with alubricant. However, manufacturing of such conventional autoclavablestoppers require multiple steps and generate a lot of waste.Conventionally, a thermoplastic elastomer stopper based on polypropyleneblends can also be used in autoclavable syringes. The autoclavablitiy ofsuch syringes is obtained by the addition of a lot of inorganic fillersinto a stopper formulation to provide structural integrity atautoclaving temperatures. The use of inorganic fillers damages thesurface of the mold resulting in reduced efficiency and high runningcosts. Also, the presence of inorganic fillers in the compositionresults in issues associated with extractables and leachables during useand storage of syringes. Therefore, there is a need for a thermoplasticelastomeric composition for the manufacturing of syringe stoppers whichcan be autoclaved without the need for inorganic fillers.

As discussed above, a stopper of the present disclosure is made of amaterial that provides the required functional properties of a stopperwithout requiring an external surface of the stopper to be lubricated.For example, a stopper of the present disclosure may be formed of athermoplastic elastomer. In this manner, a stopper of the presentdisclosure also allows for an autoclavable stopper for a syringeassembly. In one embodiment, the thermoplastic elastomer composition ofa stopper of the present disclosure is based on high melting temperaturepolymers. For example, a melting temperature ≥170 degrees C. is requiredfor autoclavable syringes. As previously discussed, in one embodiment, astopper of the present disclosure may be formed of a thermoplasticelastomer composition including a blend of injection moldable elastomersincluding block copolymers and a high transition temperature polymer. Insome embodiments, the elastomer may include a styrene block copolymer,an olefin block copolymer, polyisoprene, and butyl rubber blended withthe high transition temperature polymers which may includeethylene-tetrafluoro-ethylene (ETFE) and fluorinated ethylene propylene(FEP) polymers. In one embodiment, the composition of a stopper of thepresent disclosure may include 30 to 65% by weight of elastomers such asbut not limited to styrene block copolymer and olefin block copolymer,10 to 35% by weight of high transition temperature polymers such as butnot limited to ethylene-tetrafluoro-ethylene, and 20-35% by weight ofother additives such as mineral oil to meet the desired processingrequirements and material properties such as hardness, tensile,viscosity, and compression set properties for a stopper for a syringeassembly application. In other embodiments, the composition of a stopperof the present disclosure contains a radiation stabilizer, anantioxidant, and/or a processing aid. A stopper of the presentdisclosure overcomes the deficiencies of conventional stoppers byproviding an injection moldable thermoplastic syringe stopper whereinthe sticktion free performance is generated by the migration to thesurface of hydrocarbon liquids such as mineral oil incorporated in thecomposition of the stopper. The high temperature stable polymer at thelevel of at least 10 to 35% by weight in the composition providesstructural integrity during autoclaving processes and any other exposureto high temperature conditions. For example, the high transitiontemperature polymers may include ethylene-tetrafluoro-ethylene (ETFE)and fluorinated ethylene propylene (FEP) polymers. As discussed above,the thermoplastic elastomer composition of a stopper of the presentdisclosure is based on high melting temperature polymers. For example, amelting temperature ≥170 degrees C. is required for autoclavablesyringes. In this manner, a stopper of the present disclosure results ina lubricant free, sticktionless, autoclavable, and injection moldablestopper while eliminating the step of an external lubrication on astopper.

Syringe assembly 10 may be used to fill syringe barrel 12 with amedication from a separate vial prior to use. For example, syringeassembly 10 may be used with non-preloaded medication kits such as adiabetes therapy kit.

Referring now to FIG. 1, the use of syringe assembly 10 to fill syringebarrel 12 with medication from a separate vial prior to use will now bedescribed. With syringe assembly 10 in the position shown in FIG. 1 andwith a needle assembly locked to distal end 32 of syringe barrel 12 andplaced in communication with a vial containing fluid, when it is desiredto aspirate or pull the fluid, such as a medication, into chamber 36 ofsyringe barrel 12, a user moves plunger rod 14 in a direction generallyalong arrow A until the desired amount of the fluid is pulled intochamber 36 of syringe barrel 12. In this manner, movement of stopper 16via plunger rod 14 in the direction generally along arrow A creates avacuum inside chamber 36 of syringe barrel 12. As the user moves stopper16 via plunger rod 14 in a direction generally along arrow A, the useractively increases the volume within chamber 36 of syringe barrel 12.Because the stopper is sized relative to syringe barrel 12 to providesealing engagement with the interior wall of syringe barrel 12, asdescribed above, and because the needle assembly locked to distal end 32of syringe barrel 12 is placed in a vial containing fluid, no air canenter into chamber 36 of syringe barrel 12 and, thus, the same number ofair molecules are located within chamber 36 as the user activelyincreases the volume within chamber 36. This decreases the pressure inchamber 36 of syringe barrel 12 relative to the air pressure outside ofsyringe barrel 12. Therefore, a vacuum, i.e., a space of lower airpressure, is created to pull the fluid, such as a medication, intochamber 36 of syringe barrel 12.

Syringe assembly 10 may also be used in a pre-filled syringe assemblyand/or an injectable syringe assembly. In this manner, the need for theuser to fill the device prior to injection is eliminated, thereby savingtime and maintaining consistent volumes for delivery. Syringe assembly10 in a pre-filled syringe application may be provided for end use witha fluid, such as a medication, contained within chamber 36 of syringebarrel 12, pre-filled by the manufacturer. In this manner, syringeassembly 10 can be manufactured, pre-filled with a medication,sterilized, and packaged in appropriate packaging for delivery, storage,and use by the end user, without the need for the end user to fill thesyringe with medication from a separate vial prior to use. In such anembodiment, syringe assembly 10 may include a cap or sealing memberdisposed at distal end 32 of syringe barrel 12 to seal a fluid, such asa medication, within chamber 36 of syringe barrel 12.

Referring to FIGS. 1 and 2A, the use of syringe assembly 10 to expel afluid, such as a medication, contained within chamber 36 of syringebarrel 12 will now be described. In such an embodiment, a fluid iscontained within chamber 36 of syringe barrel 12 and stopper 16 ispositioned adjacent proximal end 34 of syringe barrel 12 as shown inFIG. 2A. In a pre-filled syringe application, a user may first remove acap or sealing member from distal end 32 of syringe barrel 12. A usercan then attach tip 42 of syringe barrel 12 to a separate needleassembly or IV connection assembly and lockingly engage the needleassembly or IV connection assembly to tip 42 of syringe barrel 12 in aknown manner. Prior to dispensing any medication, any air trapped withinchamber 36 of syringe barrel 12 can be expelled in a known manner.

When it is desired to expel or deliver the medication contained withinsyringe barrel 12, syringe assembly 10 is grasped with the user's thumbon flange 66 of plunger rod 14 and with the user's fingers extendingaround flange 40 of syringe barrel 12. In this manner, syringe assembly10 is grasped by a user in a well known and well recognized manner.Next, the user effects a squeezing movement between the thumb on flange66 of plunger rod 14 and four fingers grasping flange 40 of syringebarrel 12, thereby causing stopper 16 via plunger rod 14 to move in adirection generally along arrow B (FIG. 1). In this manner, movement ofstopper 16 via plunger rod 14 in the direction generally along arrow Bforces a fluid contained within chamber 36 of syringe barrel 12 to beforced out outlet opening 38. The fluid can be expelled from syringebarrel 12 through outlet opening 38 into a separate needle assembly orIV assembly and into the patient.

While this disclosure has been described as having exemplary designs,the present disclosure can be further modified within the spirit andscope of this disclosure. This application is therefore intended tocover any variations, uses, or adaptations of the disclosure using itsgeneral principles. Further, this application is intended to cover suchdepartures from the present disclosure as come within known or customarypractice in the art to which this disclosure pertains and which fallwithin the limits of the appended claims.

What is claimed is:
 1. A stopper for a syringe assembly, the stopper comprising a thermoplastic elastomer, wherein an outer surface of the stopper is non-lubricated and wherein the viscosity of the thermoplastic elastomer at 205 degrees C. is ≥70 Pa·s at 1,000 s⁻¹ shear rate, ≥12.0 Pa·s at 10,000 s⁻¹ shear rate, and ≥3.0 Pa·s at 50,000 s⁻¹ shear rate.
 2. The stopper of claim 1, wherein the compression set of the thermoplastic elastomer is ≤50% when measured at 25% compression for 22 hrs at 70 degrees C.
 3. The stopper of claim 1, wherein the hardness of the thermoplastic elastomer is approximately 40-70 Shore A.
 4. A syringe assembly, comprising: a syringe barrel having a proximal end, a distal end, and a sidewall extending therebetween and defining a chamber having an interior, the syringe barrel formed of a first material; a stopper slidably disposed within the interior of the chamber of the syringe barrel, the stopper sized relative to the interior of the chamber of the syringe barrel to provide sealing engagement with the sidewall of the syringe barrel, the stopper formed of a second material different than the first material, wherein the second material does not contain more than 4% of the first material; and a plunger rod having a first end engageable with a portion of the stopper.
 5. The syringe assembly of claim 4, wherein the second material does not contain more than 1.5% of the first material.
 6. The syringe assembly of claim 4, wherein the second material does not contain more than 1% of the first material.
 7. The syringe assembly of claim 4, wherein the viscosity of the thermoplastic elastomer at 205 degrees C. is ≥70 Pa·s at 1,000 s⁻¹ shear rate, ≥12.0 Pa·s at 10,000 s⁻¹ shear rate, and ≥3.0 Pa·s at 50,000 s⁻¹ shear rate.
 8. A stopper for a syringe assembly, the stopper comprising: a lower portion; a roof portion, the roof portion having a first thickness; and a shear element disposed adjacent the roof portion, the shear element having a second thickness, wherein the second thickness of the shear element is less than 52% and greater than 36% of the first thickness of the roof portion.
 9. The stopper of claim 8, wherein the second thickness of the shear element is approximately 44% of the first thickness of the roof portion.
 10. The stopper of claim 8, further comprising a catch can element having a receiving volume.
 11. The stopper of claim 8, wherein the stopper is formed from a thermoplastic elastomer having a viscosity at 205 degrees C. which is ≥70 Pa·s at 1,000 s⁻¹ shear rate, ≥12.0 Pa·s at 10,000 s⁻¹ shear rate, and ≥3.0 Pa·s at 50,000 s⁻¹ shear rate.
 12. A stopper for a syringe assembly, the stopper comprising: a lower portion; a roof portion, the roof portion having a first thickness; a shear element disposed adjacent the roof portion, the shear element having a second thickness, wherein the second thickness of the shear element is less than 52% and greater than 36% of the first thickness of the roof portion; and a catch can element having a receiving volume.
 13. The stopper of claim 12, wherein the stopper is formed from a thermoplastic elastomer having a viscosity at 205 degrees C. which is ≥70 Pa·s at 1,000 s⁻¹ shear rate, ≥12.0 Pa·s at 10,000 s⁻¹ shear rate, and ≥3.0 Pa·s at 50,000 s⁻¹ shear rate.
 14. A stopper for a syringe assembly, the stopper comprising an elastomeric body, wherein the compression set of the elastomeric body is ≤50% when measured at 25% compression for 22 hours at 70 degrees C., wherein the hardness of the elastomeric body is 40-70 Shore A, wherein the viscosity of the elastomeric body at 205 degrees C. is ≥115 Pa·s at 1,000 s⁻¹ shear rate, ≥25 Pa·s at 10,000 s⁻¹ shear rate, and ≥5 Pa·s at 50,000 s⁻¹ shear rate, and wherein the elastomeric body comprises at least an olefin block copolymer.
 15. The stopper of claim 14, wherein the compression set of the elastomeric body is ≤45% when measured at 25% compression for 22 hours at 70 degrees C.
 16. The stopper of claim 14, wherein the compression set of the elastomeric body is 35%-45% when measured at 25% compression for 22 hours at 70 degrees C.
 17. The stopper of claim 14, wherein the hardness of the elastomeric body is 51-61 Shore A.
 18. The stopper of claim 14, wherein the viscosity of the elastomeric body is 115-210 Pa·s at 1,000 s⁻¹ shear rate.
 19. The stopper of claim 14, wherein the viscosity of the elastomeric body is 165 Pa·s at 1,000 s⁻¹ shear rate.
 20. The stopper of claim 14, wherein the viscosity of the elastomeric body is 25-35 Pa·s at 10,000 s⁻¹ shear rate.
 21. The stopper of claim 14, wherein the viscosity of the elastomeric body is 30 Pa·s at 10,000 s⁻¹ shear rate.
 22. The stopper of claim 14, wherein the viscosity of the elastomeric body is 5-9 Pa·s at 50,000 s⁻¹ shear rate.
 23. The stopper of claim 14, wherein the viscosity of the elastomeric body is 7 Pa·s at 50,000 s⁻¹ shear rate.
 24. A stopper for a syringe assembly, the stopper comprising an elastomeric body, wherein the compression set of the elastomeric body is ≤45% when measured at 25% compression for 22 hours at 70 degrees C., wherein the hardness of the elastomeric body is 40-70 Shore A, and wherein the viscosity of the elastomeric body at 205 degrees C. is ≥115 Pa·s at 1,000 s⁻¹ shear rate, ≥25 Pa·s at 10,000 s⁻¹ shear rate, and ≥5 Pa·s at 50,000 s⁻¹ shear rate.
 25. The stopper of claim 24, wherein the compression set of the elastomeric body is 35%-45% when measured at 25% compression for 22 hours at 70 degrees C.
 26. The stopper of claim 24, wherein the viscosity of the elastomeric body is 115-210 Pa·s at 1,000 s⁻¹ shear rate.
 27. The stopper of claim 24, wherein the viscosity of the elastomeric body is 165 Pa·s at 1,000 s⁻¹ shear rate.
 28. The stopper of claim 24, wherein the viscosity of the elastomeric body is 25-35 Pa·s at 10,000 s⁻¹ shear rate.
 29. The stopper of claim 24, wherein the viscosity of the elastomeric body is 30 Pa·s at 10,000 s⁻¹ shear rate.
 30. The stopper of claim 24, wherein the viscosity of the elastomeric body is 5-9 Pa·s at 50,000 s⁻¹ shear rate.
 31. The stopper of claim 24, wherein the viscosity of the elastomeric body is 7 Pa·s at 50,000 s⁻¹ shear rate.
 32. A syringe assembly, comprising: a syringe barrel having a proximal end, a distal end, and a sidewall extending therebetween and defining a chamber having an interior; a stopper disposed within the interior of the syringe barrel, the stopper comprising an elastomeric body, wherein the compression set of the elastomeric body is ≤50% when measured at 25% compression for 22 hours at 70 degrees C., wherein the viscosity of the elastomeric body at 205 degrees C. is ≥115 Pa·s at 1,000 s⁻¹ shear rate, ≥25 Pa·s at 10,000 s⁻¹ shear rate, and ≥5 Pa·s at 50,000 s⁻¹ shear rate, and wherein the elastomeric body comprises at least an olefin block copolymer; and a plunger rod having a first end engageable with a portion of the stopper.
 33. The syringe assembly of claim 32, wherein the compression set of the elastomeric body is ≤45% when measured at 25% compression for 22 hours at 70 degrees C.
 34. The syringe assembly of claim 32, wherein the compression set of the elastomeric body is 35%-45% when measured at 25% compression for 22 hours at 70 degrees C.
 35. The syringe assembly of claim 32, wherein the hardness of the elastomeric body is 51-61 Shore A.
 36. The syringe assembly of claim 32, wherein the viscosity of the elastomeric body is 115-210 Pa·s at 1,000 s⁻¹ shear rate.
 37. The syringe assembly of claim 32, wherein the viscosity of the elastomeric body is 165 Pa·s at 1,000 s⁻¹ shear rate.
 38. The syringe assembly of claim 32, wherein the viscosity of the elastomeric body is 25-35 Pa·s at 10,000 s⁻¹ shear rate.
 39. The syringe assembly of claim 32, wherein the viscosity of the elastomeric body is 30 Pa·s at 10,000 s⁻¹ shear rate.
 40. The syringe assembly of claim 32, wherein the viscosity of the elastomeric body is 5-9 Pa·s at 50,000 s⁻¹ shear rate.
 41. The syringe assembly of claim 32, wherein the viscosity of the elastomeric body is 7 Pa·s at 50,000 s⁻¹ shear rate.
 42. A stopper for a syringe assembly, the stopper comprising an upper portion, a lower portion, and a middle portion extending between the upper portion and the lower portion, the upper portion, the lower portion, and the middle portion defining an interior cavity, wherein at least one arm element is provided within the interior cavity in the upper portion of the stopper, the stopper further comprising an elastomeric body, wherein the compression set of the elastomeric body is ≤45% when measured at 25% compression for 22 hours at 70 degrees C., wherein the viscosity of the elastomeric body at 205 degrees C. is ≥115 Pa·s at 1,000 s⁻¹ shear rate, ≥25 Pa·s at 10,000 s⁻¹ shear rate, and ≥5 Pa·s at 50,000 s⁻¹ shear rate, and wherein the elastomeric body comprises at least an olefin block copolymer. 